ORGANIC LETTERS
Mercuric Triflate-Catalyzed Reaction of Propargyl Acetates with Water Leading Vinyl Ketones
2006 Vol. 8, No. 3 447-450
Hiroshi Imagawa, Yumiko Asai, Hiroto Takano, Hitomi Hamagaki, and Mugio Nishizawa* Faculty of Pharmaceutical Sciences, Tokushima Bunri UniVersity, Yamashiro-cho, Tokushima 770-8514, Japan
[email protected] Received November 11, 2005
ABSTRACT
Reaction of propargyl acetate with water catalyzed by Hg(OTf)2 afforded vinyl ketone as the major product along with a dimeric vinyl mercuric product and normal hydration products in small amounts. The reaction is an alternative to the Meyer−Schuster and Rupe rearrangement applicable to primary alcohols, although the mechanism is entirely different.
Acid-catalyzed rearrangement of propargyl alcohol to an R,βunsaturated ketone is known as the Meyer-Schuster and Rupe rearrangement. Unfortunately, this reaction has only been usable for tert- and sec-alcohols.1 In this communication, we describe the reaction of propargyl acetate and water to give vinyl ketones under very mild conditions, catalyzed by mercury(II) trifluoromethanesulfonate [mercuric triflate, hereafter referred to as Hg(OTf)2], as an alternative to the Meyer-Schuster and Rupe rearrangement applicable to primary alcohols, although the mechanism is entirely different. Conversion of primary propargyl alcohols to vinyl ketones was reported by Yadav using 6 equiv of Hg(OAc)2 followed by H2S treatment2a and by Alami using CF3CO2H at 100 °C.2b Trahanovsky also reported enone synthesis by pyrolysis of propargyl esters at very high temperature (around (1) (a) Meyer, K. H.; Schuster, K. Chem. Ber. 1922, 55, 819-821. (b) Rupe, H.; Kambli, E. HelV. Chim. Acta 1926, 9, 672. (c) Swaminathan, S.; Narayanan, K. V. Chem. ReV. 1971, 71, 429-438. (d) Chabardes, P. Tetrahedron Lett. 1988, 29, 6253-6256. (e) Narasaka, K.; Kusama, H.; Hayashi, Y. Chem. Lett. 1991, 1413-1416. (f) Narasaka, K.; Kusama, H.; Hayashi, Y. Tetrahedron 1992, 48, 2059-2068. (g) Mercier, C.; Chabardes, P. Pure Appl. Chem. 1994, 66, 1509-1518. (h) Suzuki, T.; Tokunaga, M.; Wakatsuki, Y. Tetrahedron Lett. 2002, 43, 7531-7533. (i) Cadierno, V.; Diez, J.; Garcia-Garrido, S. E.; Gimeno, J. Chem. Commun. 2004, 27162717. 10.1021/ol0527431 CCC: $33.50 Published on Web 01/10/2006
© 2006 American Chemical Society
650 °C).2c We originally developed Hg(OTf)2 as a highly efficient olefin cyclization agent,3 and we applied it to the synthesis of polycyclic terpenoids.4 Recently, we found that the Hg(OTf)2 and Hg(OTf)2-tetramethylurea (TMU) complexes showed highly efficient catalytic activity in several (2) (a) Yadav, J. S.; Prahlad, V.; Muralidhar, B. Synth. Commun. 1997, 27, 3415-3418. (b) Olivi, N.; Thomas, E.; Peyrat, J. F.; Alami, M.; Brion, J. D. Synlett 2004, 2175-2179. (c) Trahanovsky, W. S.; Mullen, P. M. J. Am. Chem. Soc. 1972, 94, 5086-5087. (3) (a) Nishizawa, M.; Takenaka, H.; Nishide, H.; Hayashi, Y. Tetrahedron Lett. 1983, 24, 2581-2584. (b) Nishizawa, M.; Morikuni, E.; Asoh, K.; Kan, Y.; Uenoyama, K.; Imagawa, H. Synlett 1995, 169-170. (c) Nishizawa, M. Studies in Natural Product Chemistry. In StereoselectiVe Synthesis, Part A; Rahman, A. u., Ed.; Elsevier: Amsterdam, Holland, 1988; Vol. 1, pp 655-676. (d) Nishizawa, M. J. Synth. Org. Chem. Jpn. 1999, 57, 677-688. (4) (a) Nishizawa, M.; Takenaka, H.; Hirotsu, K.; Higuchi, T.; Hayashi, Y. J. Am. Chem. Soc. 1984, 106, 4290-4291. (b) Nishizawa, M.; Takenaka, H.; Hayashi, Y. J. Am. Chem. Soc. 1985, 107, 522-523. (c) Nishizawa, M.; Takenaka, H.; Hayashi, Y. J. Org. Chem. 1986, 51, 806-813. (d) Nishizawa, M.; Yamada, H.; Hayashi, Y. Tetrahedron Lett. 1986, 27, 187190. (e) Nishizawa, M.; Yamada, H.; Hayashi, Y. J. Org. Chem. 1987, 52, 4878-4884. (f) Nishizawa, M.; Takao, H.; Kanoh, N.; Asoh, K.; Hatakeyama, S.; Yamada, H. Tetrahedron Lett. 1994, 35, 5693-5696. (g) Nishizawa, M.; Morikuni, E.; Takeji, M.; Asoh, K.; Hyodo, I.; Imagawa, H.; Yamada, H. Synlett 1996, 927-928. (h) Nishizawa, M.; Takao, H.; Iwamoto, Y.; Yamada, H.; Imagawa, H. Synlett 1998, 76-78. (i) Nishizawa, M.; Imagawa, H.; Hyodo, I.; Takeji, M.; Morikuni, E.; Asoh, K.; Yamada, H. Tetrahedron Lett. 1998, 39, 389-392.
reactions including hydroxylative 1,6-enyne cyclization to give exomethylene five-membered ring products,5 cyclization of 1-alkyn-5-ones leading to 2-methylfurans,6 arylalkyne cyclization leading to dihydronaphthalene derivatives,7 and biomimetic tandem cyclization of aryl-ene-yne derivatives to give polycarbocycles.8 We have also reported that Hg(OTf)2‚(TMU)2 showed highly efficient catalytic activity for the hydration of terminal alkynes to give methyl ketones under very mild conditions.9 That reaction is far more efficient than the more commonly used general procedure, which employs a significant amount of HgO and H2SO4 in refluxing aqueous methanol.10 It is well-known that the hydration of internal alkyne bonds produces a regioisomeric mixture of ketones, and thus, it is a practically useless reaction. Consequently, we tried to control the regioselectivity of Hg(OTf)2-catalyzed hydration of internal alkynes by using neighboring group participation and examined the reaction of propargyl acetate 1 with water in the presence of a catalytic amount of Hg(OTf)2 (Scheme 1). Contrary to
Scheme 1
expectation, the major product was not the expected hydration products 4 or 5 but was vinyl ketone 2.11a,b A strange dimeric vinyl mercuric product 3 was also detected in low yield.11c To characterize the reaction, we first examined a reaction of propargyl acetate 1 with 1.5 equiv of H2O in the presence of Hg(OTf)2 (5 mol %) in acetonitrile at room temperature.12 The reaction was completed within 4 h, and vinyl ketone 2 was obtained in 84% yield after column chromatography on silica gel. The yield before purification, as measured by NMR, was 82%. Additional products included the dimeric (5) Nishizawa, M.; Yadav, V. K.; Skwarczynski, M.; Takao, H.; Imagawa, H.; Sugihara, T. Org. Lett. 2003, 5, 1609-1611. (6) Imagawa, H.; Kurisaki, T.; Nishizawa, M. Org. Lett. 2004, 6, 36793681. (7) Nishizawa, M.; Takao, H.; Yadav, V. K.; Imagawa, H.; Sugihara, T. Org. Lett. 2003, 5, 4563-4565. (8) (a) Imagawa, H.; Iyenaga, T.; Nishizawa, M. Org. Lett. 2005, 7, 451453. (b) Imagawa, H.; Iyenaga, T.; Nishizawa, M. Synlett 2005, 703-705. (9) Nishizawa, M.; Skwarczynski, M.; Imagawa, H.; Sugihara, T. Chem. Lett. 2002, 12-13. (10) (a) Thomas, R. J.; Campbell, K. N.; Hennion, G. F. J. Am. Chem. Soc. 1938, 60, 718-720. (b) Stacy, G. W.; Mikulec, R. A. Org. Synth. 1963, 4, 13-15. (11) (a) Murai, A.; Abiko, A.; Shimada, N.; Masamune, T. Tetrahedron Lett. 1984, 25, 4951-4954. (b) Satoh, T.; Kumagawa, T.; Yamakawa, K. Tetrahedron Lett. 1986, 27, 2471-2474. (c) Szemenyei, D.; Steichen, D.; Byrd, J. E. J. Mol. Cat. 1977, 2, 105-117. (d) Choudary, B. M.; Prasad, A. D.; Swapna, V.; Valli, V. L. K.; Bhuma, V. Tetrahedron 1992, 48, 953962. (e) Cahiez, G.; Bernard, D.; Normant, J. F. Synthesis 1977, 130-133. 448
mercuric product 3 (1% yield) as well as ketones 4 (4%) and 5 (4%) (Table 1, entry 1).11 The effects of varying the
Table 1. Hg(OTf)2-Catalyzed Reaction of 1 and H2Oa yield (%)b
entry
Hg(OTf)2 (mol %)
solvent
H2O equiv
2
3
4
5
1 2 3 4 5 6 7 8 9
5 5 5 5 5 5 5 1 5c
CH3CN CH3CN CH3CN CH3CN CH2Cl2 C6H5CH3 CH3NO2 CH3CN CH3CN
1.5 1.1 3.0 5.0 1.5 1.5 1.5 1.5 1.5
82 71 66 53 14 16 64 16 74
1 2 4 5 2 2
4 3 3 4
4 4 9 14
1 4
4
3
3
1
1 12 72 68 75 5
a Reactions were carried out at room temperature for 4 h. b NMR yield using mesitylene as the internal standard. c Reaction in the presence of TMU (5 mol %).
amount of water on the yield of vinyl ketone were investigated at 1.5, 1.1, 3, and 5 equiv, and the 1.5 equiv was shown to be the best (Table 1, entries 1-4). Water insoluble dichloromethane and toluene were shown to be useless as solvent affording significant amounts of starting material (Table 1, entries 5 and 6), and nitromethane was not as good as acetonitrile (Table 1, entry 7). One mol % of catalyst was not enough to complete the reaction (Table 1, entry 8). Reaction in the presence of TMU (5 mol %) produced a higher quantity of 3, and the yield of vinyl ketone 2 was 74% at room temperature for 4 h (Table 1, entry 9). Next, we investigated the reactions of a variety of 4-cyclohexyl-2-butynyl esters 6a-k (Scheme 2). By comparison with acetate 1 (Table 1, entry 1), 2-methylpropionate 6a was converted to enone 2 in lower yield (73%) along with 3 (2%) and ketones 7a (5%) and 8a (5%) (Table 2, entry 1). Pivalate 6b, methoxy acetate 6c, and monochloroacetate 6d also produced enone 2 in moderate yield within several hours (Table 2, entries 2-4). p-Methoxybenzoate 6e, p-nitrobenzoate 6f, and pentafluorobenzoate 6g formed product 2 only in poor to moderate yield after 24 h (Table 2, entries 5-7). Surprisingly, benzoate 6h and 2,4,6trichlorobenzoate 6i produced no trace of products at all (Table 2, entries 8 and 9). On the other hand, formate 6j produced 2 in 51% yield along with 3 (2%) and ketones 7j (2%) and 8j (4%) (Table 2, entry 10). The mother alcohol 6k was entirely inert under the standard reaction conditions, and all starting materials were recovered (Table 2, entry 11). (12) Typical experimental procedure is as follows. To a stirred solution of propargyl acetate 1 (194 mg, 1.0 mmol) and water (27 mg, 1.5 mmol, 1.5 equiv) in acetonitrile (9.5 mL) was added 0.5 mL of 0.1 M Hg(OTf)2 (0.5 mL, 5 mol %) in acetonitrile at room temperature under argon, and the mixture was allowed to stir at the same temperature for 4 h. After addition of aqueous NaHCO3, the organic material was extracted with ether. Dried and concentrated material was subjected to a column chromatography on silica gel using pentane and ether as eluent to give enone 2 (128 mg, 84% yield, NMR yield 82%) and a mixture of dimeric mercury compound 3 (NMR yield 1%, determined by using mesitylene as an internal standard), ketones 4 (NMR yield 2%), and ketone 5 (NMR yield 6%).
Org. Lett., Vol. 8, No. 3, 2006
Scheme 2
Table 3. Hg(OTf)2-Catalyzed Reaction of Acetate with H2O
Together, these results indicated that the reactions were affected by neither electronic nor steric factors of leaving groups, and we concluded that acetate is the leaving group of choice. We then examined the reaction of 2-decanoyl acetate (9) with 1.5 equiv of water in CH3CN at room temperature for 3.5 h in the presence of 5 mol % Hg(OTf)2. Enone 1011a was obtained in 70% yield (as measured by NMR; isolated yield was 59%) along with dimeric mercuric product 11 (2%) and a mixture of hydrated ketones (7%) (Table 3). Phenylpropargyl acetate 12 formed enone 132c,11a,11d in 51% yield (isolated yield 53%), and 3-oxo-3-phenylpropanoyl acetate (18%), but no dimeric mercuric product, was detected. Reaction of propargyl acetate containing tert-alcohol 14 afforded only Meyer-Schuster product 15 in 76% yield (isolated yield 74%), and the acetate group did not affect the reaction. Reaction of secondary acetate 16 took place smoothly to give (E)-enone 17 selectively in 84% yield (isolated yield 80%) along with dimeric mercuric product 18 (2% yield). Stereochemistries of 17 and 18 were established to be E and Z, respectively, on the basis of nuclear Overhauser effect (NOE) experiments. When the same reaction was carried out using 1 mol % of Hg(OTf)2, enone 17 was obtained in 88% yield after 114 h. The reaction of tert-acetate 19 was completed within 6 min and afforded enone 2011e in 67% yield (isolated yield 60%) along with an enyne 21 in 13% yield. When water was added to the mixture of 19 and Hg(OTf)2, the yield of 20 and 21 changed to 15% and 60%, respectively, as measured by NMR. When diacetate 22 was treated with 5 mol % of Hg(OTf)2 and H2O (1.5 equiv), enones 23 and 24 were obtained in 70% yield (isolated yield 61%) and 18% yield (isolated yield 15%), respectively, along with a 1:5 mixture of dimeric products
Table 2. Hg(OTf)2-Catalyzed Reaction of 6 with H2Oa entry
R
time (h)
1 2 3 4 5 6 7 8 9 10 11
a: COCH(CH3)2 b: COC(CH3)3 c: COCH2OCH3 d: COCH2Cl e: COC6H4-p-OCH3 f: COC6H4-p-NO2 g: COC6F5 h: COC6H5 i: COC6H2-2,4,6-Cl3 j: COH k: H
2 2 4 4 24 24 24 24 24 4 24
yield (%)b 2
3
7
8
73 67 68 61 30 53 14
2 2 3 3
5 16 4 7 5 10
5 6 2 1 1
51
2
2
4
3 1
6
2 8 64 18 65 100 100 14 100
a Reaction with 1.5 equiv of H O in CH CN at room temperature. b NMR 2 3 yield using mesitylene as an internal standard.
Org. Lett., Vol. 8, No. 3, 2006
a NMR yield using mesitylene as an internal standard. b NMR yield using naphthalene as an internal standard. c Isolated yield.
25 and 26 in 3% yield that was difficult to separate. Stereochemistries of 24 and 26 were established to be E and Z, respectively, on the basis of NOE experiments. Taken together, these results are consistent with the following mechanism (Scheme 3). The reaction is initiated by π-complexation of alkyne with Hg(OTf)2, as shown in 27. Oxonium cation 28 is attacked by water to generate intermediate 29 along with TfOH. Protonation of 29 forms alternative oxonium cation 30, which undergoes demercuration to produce the second intermediate 31 and the catalyst Hg(OTf)2. A 6π electrocyclic reaction should yield the enone 32, along with acetic acid 33. If water attacks carbon 3 of the oxonium cation as indicated in 34, an alternate intermediate 35 could form. The corresponding ketone 36 cannot be demercurated because protonation would convert it to an unstable primary cation. However, 36 may react slowly with a second propargyl acetate molecule, creating another oxonium cation 37, which becomes the stable vinyl mercury product 38. Therefore, this process contains a novel suicide mechanism for the catalyst Hg(OTf)2. This could explain why we could not achieve the very high catalytic turnover for vinyl ketone formation that we observed for 449
Scheme 3
In summary, we have developed a novel reaction between propargyl acetate and water catalyzed by Hg(OTf)2 to produce synthetically useful conjugated ketones under very mild conditions. The reaction behaves like a variation of the Meyer-Schuster and Rupe rearrangement, but it is applicable to primary alcohols. Toxicity of organomercuric compounds is a serious concern, particularly with respect to their use in industrial synthetic application. Although, CH3HgCl and (CH3)2Hg are extremely dangerous and can cause serious damage to the central nervous system, most organomercuric compounds are not that toxic. Phenylmercuric acetate used to be employed as agrochemicals for rice fields, and mercurochrome is an excellent antiseptic for wounds. It is important to distinguish between useful mercuric compounds and the highly toxic methylmercuric chloride. Acknowledgment. This study was financially supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of the Japanese Government. Supporting Information Available: Spectroscopic data. This material is available free of charge via the Internet at http://pubs.acs.org.
enyne cyclization,5 arylyne cyclization,7 and biomimetic tandem cyclization.8
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